Department of Biomedical Science and Technology, Konkuk University, 1 Hwayangdong, Gwangjin-gu, Seoul, Korea.
Nat Rev Neurol. 2010 Dec;6(12):702-6. doi: 10.1038/nrneurol.2010.145. Epub 2010 Oct 12.
Neurodegenerative disorders such as Alzheimer disease, Parkinson disease, frontotemporal dementia, Huntington disease and Creutzfeldt-Jakob disease (CJD) are characterized by progressive accumulation of protein aggregates in selected brain regions. Protein misfolding and templated assembly into aggregates might result from an imbalance between protein synthesis, aggregation and clearance. Although protein misfolding and aggregation occur in most neurodegenerative disorders, the concept of spreading and infectivity of aggregates in the CNS has, until now, been confined to prion diseases such as CJD and bovine spongiform encephalopathy. Emerging evidence, however, suggests that prion-like spreading, involving secreted proteins such as amyloid-β and cytosolic proteins such as tau, huntingtin and α-synuclein, can occur in other neurodegenerative disorders. The underlying molecular mechanisms and the therapeutic implications of the new data are discussed in this article.
神经退行性疾病，如阿尔茨海默病、帕金森病、额颞叶痴呆、亨廷顿病和克雅氏病（CJD），其特征是在特定脑区中蛋白质聚集体的进行性积累。蛋白质错误折叠和模板组装成聚集体可能是由于蛋白质合成、聚集和清除之间的失衡所致。尽管大多数神经退行性疾病中都存在蛋白质错误折叠和聚集，但聚集体在中枢神经系统中的传播和传染性的概念，直到现在，仅限于朊病毒病，如 CJD 和牛海绵状脑病。然而，新出现的证据表明，涉及分泌蛋白（如淀粉样β和细胞质蛋白（如 tau、亨廷顿蛋白和α-突触核蛋白）的朊病毒样传播可以发生在其他神经退行性疾病中。本文讨论了新数据背后的分子机制及其治疗意义。
